Cervical Dysplasia: Discussion Of Botanicals

Blood Root

The blood-red color of the sap from the roots of blood root led to its traditional use as a blood purifier. It was used as an emmenagogue, in the treatment of respiratory conditions, as a strong emetic, and for the treatment of fungal infections and ulcers. By the eighteenth century, blood root was used topically to treat indolent chancres and tumors as an ingredient in the popular “black salve,” an escharotic treatment that was used topically for the treatment of tumors. Extracts of sanguinarine, an alkaloid from the herb, have been shown to possess anti-inflammatory, antimicrobial, antioxidant, antiviral, antiproliferative, and apoptotic activities, and are under active research for the treatment of cancer. Sanguinarine, an alkaloid compound fund in blood root, is a potent inhibitor of NF-kappa B activation.’ Sanguinarine is an ingredient in dental hygiene products, for example, toothpaste, used for its antiplaque activity and in the treatment of gingivitis. There is controversy over the safety of its use in dental products, with contradictory research over whether it may cause malignant cell change and lead to the development of leukoplakia. Most studies have concluded that the extract is safe for dental use; however, at least one study concludes that it should not be used until safety can be established. One study on reproductive and developmental toxicology conducted by orally administering blood root extract to rats and rabbits concluded that the oral intake of blood root extract has no selective effect on fertility or reproduction of fetal and neonatal development in either group. The question of safety and effects of the herb on the oral mucosa remains relevant as the application to the cervix is similar in terms of direct treatment of epithelial tissue. The form used in black salve is the whole plant extract rather than isolated alkaloid for which cautions have been raised. At this time, evidence regarding the internal use of this herb for cervical dysplasia treatment is lacking, and serious caution is suggested regarding its topical use.

Bromelain

Bromelain is a complex mixture of proteinases derived from pineapple stems and fruit. Beneficial therapeutic effects of bromelain have been demonstrated in vitro, and in animal and human inflammatory disease models, including treatment of arthritis and inflammatory bowel disease, among others. Bromelain inhibits plasma exudation through inhibiting the generation of bradykinin at the inflammatory site via depletion of the plasma kallikrein system, and possibly through other mechanisms, such as inhibition of the arachidonic acid pathway. Beneficial anti-inflammatory effects have also been observed in patients suffering from HIV and cancer. In one randomized study, 36 patients with Chlamydia infections were assigned either to a tetracycline-HCl plus bromelain (250 and 40 mg, respectively, four times per day) or a doxycycline (100 mg, twice daily) treatment for a period of 14 days. After 7 days, the pathogen was eliminated in 66.7% of the patients treated with tetracycline plus bromelain and in 55.6% of the patients receiving doxycycline. After the completion of the course of therapy, an infection with Chlamydia was no longer detectable in any patient of the two groups. The clinical effectiveness of the two therapies was considered to be good or very good in all cases. Adverse effects occurred in 11% (tetracycline + bromelain) and 16% (doxycycline) of the patients. Treatment of the sexual partner (with antibiotics) was also considered essential to the success of the study.

Bromelain is an important proteolytic ingredient in the treatment of cervical dysplasia.

Calendula

Calendula flowers are indicated for the topical treatment of minor inflammations of the skin and mucosa, to assist in the healing of minor wounds, and for the treatment of burns. The most common topical applications include infusions used as washes, oil-based extractions, ointments, and the succus, or juice, which is high in enzymatic activity. Hydroalcoholic extracts have demonstrated antibacterial and antifungal activity, as well as high virucidal action. Calendula extracts have shown specific activity against herpes simplex virus, HIV, and Trichomonas. Anti-inflammatory and wound-healing effects have been demonstrated in vitro and in vivo, with topical anti-inflammatory effects attributed to the effects of the polysaccharide fractions of the plant. Other important compounds are thought to be the major anti-inflammatory triterpenoid esters in the flower heads faradiol 3-O-laurate, palmitate and myr-istate. In one study, freeze-dried extracts of St. John’s wort, calendula, chamomile, and plantain were found to suppress both inflammatory effects and leukocyte infiltration in animal models. Wound-healing effects also have been attributed to the angiogenic activity of the herb. Calendula succus is used as a wash in the escharotic treatment, and as an ingredient in other topical applications for the treatment of cervical dysplasia, particularly in suppositories for vulnerary and anti-inflammatory effects after invasive gynecologic procedures (e.g., biopsy, loop electrical excision procedure). Calendula is used topically to hasten healing by reducing inflammation through an increase in granulation. No studies were identified using calendula for the treatment of human papillomavirus infection. Some concern exists as to whether use of calendula can lead to sensitization and potential for developing contact dermatitis; however, this risk appears to be insignificant, and in fact, the herb has been found to be highly effective for the prevention of acute dermatitis of grade 2 or higher in patients undergoing postoperative irradiation for breast cancer. Known sensitivity to the Composita family can theoretically pose this risk; however, adverse effects from topical use have not been widely observed despite its widespread use.

Goldenseal

Goldenseal is one of the five top-selling herbs in the United States, yet little scientific evidence is available regarding its efficacy. Many herbalists consider goldenseal an indispensable antimicrobial herb, in addition to it being anti-inflammatory, immune enhancing, and antiproliferative, effects largely attributed the herb’s berberine content. These actions form the basis for its topical use in the treatment of cervical dysplasia. Although no research has been done specifically on the treatment of human papillomavirus with goldenseal, the herb has shown broad antimicrobial effects, with specific effects against Chlamydia, S. aureus, E. coli, V. cholera, Trichomonas vaginalis, Giardia lamblia, and H. pylori, as well as other organisms. It has also demonstrated antifungal effects against numerous organisms, including Candida albicans. Its anti-inflammatory effects are attributed to its ability to interfere with the arachidonic acid pathway and cyclooxy-genase generation, particularly COX-2 regulation and inhibition of phospholipase enzymes.S,S Berberine was demonstrated in vitro to have antiproliferative effects via inhibition of protein, DNA, RNA, and lipid synthesis in specific tumor cell lines; however, these effects were not borne out in vivo. Berberine extracts were able to induce apoptosis during S-phase of the cell cycle, and have demonstrated the ability to activate antitumor macro-phages, in addition to several other anticancer in vitro effects. In a study of the immunomodulatory effects of 6 weeks of orally administered goldenseal, the treated group showed an increase in the primary IgM response during the first 2 weeks of treatment, suggesting that goldenseal may enhance immune function by increasing antigen-specific immunoglobulin production. Although direct effects against human papillomavirus are unknown, use of this herb in suppositories may be effective for reducing comorbid infection, allowing the body to direct its immune activity against the human papillomavirus, and through eliminating overgrowth of pathogenic microorganisms, allow the body to restore a healthy vaginal environment that may be less likely to support the growth of human papillomavirus. As with other herbs, goldenseal’s anti-inflammatory effects may be beneficial in reducing cervical irritation or inflammation that might contribute to the development of dysplasia.

Licorice is used in the treatment of cervical dysplasia, both topically and orally, for its antimicrobial, anti-inflammatory, immunomodulating, and antitumorigenic effects. It has been shown to inhibit prostaglandin and leukotriene synthesis in a similar way to corticosteroids such as prednisone. It has also demonstrated specific antiviral activity against a wide range of viruses associated with chronic illness and latent infection. In one study, treatment of cells latently infected with Kaposi’s sarcoma-associated herpes virus (KSHV) with glycyrrhizic acid (GL), a component of licorice, reduced synthesis of a viral latency protein and induced apoptosis of infected cells. This finding suggests a novel way to interrupt latency. GL demonstrated activity against EBV replication in superinfected cells in a dose-dependent fashion in a novel way that differed that of the nucleoside analogs that inhibit viral DNA polymerase. The mechanism underlying licorice’s antiviral and antitumorigenic effects is poorly understood. One study looking at mechanisms was able to demonstrate that glycyrrhetinic acid (GA), an aglycone of GL, stimulates NO production and is able to upregulate iNOS expression through NF-kB transactiva-tion in macrophages. In vitro studies have demonstrated activity against HIV virus. Licorice and its extracts have been shown to improve immune function in HIV patients by stabilizing helper and T-lymphocyte counts in comparison with the control groups in one study. In another study, it increased T-helper cell levels, improved helper / suppressor cell ratios and improved liver function, and stopped the progression of HIV-positive patients to AIDS in comparison with the control group that did progress on to AIDS. In yet another study, it showed a reduction of P24 antigen, an indicator of viral load. The antiviral properties of these compounds have been found to be effective in hepatitis B and C where intravenous preparation has resulted in up to 40% going into complete remission. Topical use of licorice extract on herpes reduces the healing time and pain associated with both genital herpes and cold sores. Another component of licorice, deoxoglycyrrhetol (DG), also showed a remarkable improvement in anti-inflammatory, antiallergic, and antiulcer activities in animal experiments. Immunomodulating effects of GL, GA, and DG derivatives, which induce interferon-gamma and some other cytokines, have been demonstrated in relation with their antiviral activities. Glycyrrhizin has been used for the treatment of chronic viral hepatitis. One study evaluated the mechanism by which glycyrrhizin inhibits complement. Glycyrrhizin inhibited the cytolytic activity of complement via the activation of both the classical and alternative pathways, whereas it had no effect on immune adherence, suggesting that it blocks C5 or a later stage of the complement cascade. Further analysis revealed that glycyrrhizin inhibits the lytic pathway in which the membrane attack complex (MAC) is formed. This mechanism suggests that glycyrrhizin may prevent tissue injury caused by MAC not only in chronic hepatitis, but in many autoimmune and inflammatory diseases as well. Topical treatment of herpes simplex virus blisters with licorice extract may improve healing and prevent recurrence. Although no studies were identified on the treatment of human papillomavirus with licorice or its extracts, other viral studies, as well as the herb’s traditional uses, suggest that investigation into such use may be promising. See Plant Profiles: Licorice for warnings and contraindications to regular internal use of this herb.

Lomatium

Lomatium has been used historically by Native Americans, mostly as a treatment for respiratory illness. It is considered antiviral, antibacterial, and antiseptic and is commonly used by naturopathic physicians and taken internally, for the treatment of cervical dysplasia. Lomatium has demonstrated in vivo and in vitro efficacy against human papillomavirus and herpes simplex virus and has been investigated for its effects against fjjv. Its use has been described for the treatment of “slow” viruses with accompanying immune depression, and may commonly be combined with other herbs with immune-building effects. Lomatium is also used topically for gum and mouth inflammations and as a douche for vaginal infections.

Marshmallow

Marshmallow root is a polysaccharide-rich herb, loved by herbalists for its soothing, demulcent properties. The mucilaginous quality of aqueous extracts and moistened powdered herb provides a protective, soothing coating to mucosa; thus, it is commonly included in preparations for throat, GI, and vaginal mucosal irritation. Several studies have found the herb efficacious, in combination with other specific herbs, for the treatment of cough, and the herb is approved for use by the German Commission E for the treatment of irritation of the oral and pharyngeal mucosa and mild inflammation of the gastric mucosa. The root also exerts immune-enhancing and antibacterial effects.

The tincture and powdered forms of this herb are used topically for the treatment of inflammatory mucosal conditions, usually of the oral and pharyngeal mucosa but also as an ingredient in vaginal suppositories. Local anesthetic, antibacterial, and antifungal activities also have been ascribed to the sesquiterpene fraction of the herb. It is a common ingredient in oral hygiene preparations, for example, ointments, dentifrices, and toothpastes. It is approved by the German Commission E for the topical treatment of mild inflammations of the oral and pharyngeal mucosa. Low Dog states that “No data have been found to document antiviral activity [of myrrh], but in light of the antiseptic, cyto-protective, and anti-inflammatory effects of the herb it may offer some benefit” in the treatment of cervical dysplasia.

Both oregano and thyme essential oils are regularly included in vaginal suppositories for the treatment of vaginal infections, including human papillomavirus infection. They are also used topically as antimicrobials against numerous bacterial and fungal infections, for which they are considered highly effective ingredients. One study reports on the efficacy of thyme as an antibacterial, and in another study oregano and clove oils were diluted and examined for their activity against enveloped and non-enveloped RNA and DNA viruses. Olive oil was also included as a control. Viruses were incubated with oil dilutions and enumerated by plaque assay. Antiviral activity of oregano and clove oils was demonstrated on two enveloped viruses of both the DNA and RNA types and the disintegration of virus envelope was visualized by negative staining using transmission electron microscopy. Care should be taken in the use of essential oils topically; used undiluted (neat) they can be irritating to sensitive tissues such as cervical or vaginal mucosa.

Reishi

Reishi is a medicinal fungus with a long history of use as a Chinese folk medicine for promotion of health and longevity. Numerous in vitro and animal studies have demonstrated antitumor and immunomodulatory effects of Reishi mushrooms. An OVID search for this herb yielded over 900 papers reporting on in vivo and in vitro effects. A wide range of antitumor and immunomodulatory mechanisms have been purported and observed, with the water extract and the polysaccharide fraction, as well as the alcohol extract or the triterpene fraction, and include enhanced function of antigen-presenting cells, the mononuclear phagocyte system, humoral immunity, and cellular immunity. Reishi polysaccharide peptide (Gl-PP) has demonstrated antitumor effects in mice and potential antiangiogenesis, a reduction of Bcl-2 antiapoptotic protein expression and an increase of Bax proapoptotic protein expression; therefore, inducing cell apoptosis might be one of the mechanisms of action in inhibition of human carcinoma cells. High doses of Gl-PP resulted in a decrease in the secreted vascular endothelial growth factor (VEGF). Taken together, these findings support the hypothesis that the key attribute of the antiangiogenic potential of Gl-PP is that it may directly inhibit vascular endothelial cell proliferation or indirectly decrease growth factor expression of tumor cells. It has been demonstrated that G. lucidum induces apoptosis, inhibits cell proliferation, and suppresses cell migration of highly invasive human prostate cancer cells PC-3. Experimental results on cell-mediated immunity showed that G. lucidum could increase the percentage of CD5+, CD4+, and CD8+ T lymphocytes. Experimental results on humoral immunity in horses showed that G. lucidum could help horses to produce a significantly higher quantity of specific antibodies in a shorter time. Although the pharmacology and clinical application of water extracts of G. lucidum have been extensively documented, little is known regarding its alcohol extract. In the present study, the antitumor effect of an alcohol extract was investigated using MCF-7 breast cancer cells. The extract inhibited cell proliferation in a dose- and time-dependent manner, which might be mediated through upregulation of p21 / Wafl and downregulation of cyclin D1. Furthermore, this compound can directly induce apoptosis in MCF-7 cells, which might be mediated through upregulation of a pro-apoptotic Bax protein and not by the immune system. There are likely multiple mechanisms underlying the antitumor effects of G. lucidum. G. lucidum also demonstrated antioxidant activity, free-radical scavenging, and chelating abilities. No specific studies were identified on the use of G. lucidum for the treatment of human papillomavirus infection or cervical dysplasia; however, given the mechanisms of action of this herb, this may be a promising area of research, and certainly merits consideration of this herb in an immune-enhancing protocol.

Thuja

Thuja is used by many herbalists and naturopathic physicians for the treatment of genital and anal warts, and is commonly recommended in the naturopathic treatment of cervical dysplasia for its antiviral activity. The main constituent is an essential oil consisting of α- and β-thujone, the content of which varies proportionally with the amount of ethanol used in producing the plant extract. If consumed internally, thujone can be neurotoxic, convulsant, and hallucinogenic. Long-term or excessive use of thujone-rich products can cause restlessness, vomiting, vertigo, tremors, renal damage, and convulsions. Internal use of thuja decoctions and even very small doses of thuja oil (i.e., 20 drops per day for 5 days) as an abortifacient has been associated with neurotoxicity, convulsions, and death. Additionally, thuja is associated with a substantial risk of inducing fetal malformation, and is absolutely contraindicated for use in pregnancy. No research on the short- or long-term topical use of this herb was identified. Ingestion of thuja cannot be recommended because of potential for toxicity.